Roy scored twice and added an assist while Pominville donated a marker and two assists as the Sabres beat the Penguins for the first time in five meetings.
Ryan Miller earned the victory with 24 saves.
Buffalo chased starting netminder Pittsburgh Brent Johnson with three goals on 12 shots. Marc-Andre Fleury relieved but also wasn't effective, letting in three tallies on 12 shots.
Jordan Stall and Deryk Engelland scored for Pittsburgh.